Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Ellagic Acid Supplementation Ameliorates Cisplatin-Induced Liver Injury in Mice via the Activation of Nrf2/HO-1 Pathway and the Inhibition of NF-kB Pathway

Version 1 : Received: 1 October 2023 / Approved: 2 October 2023 / Online: 2 October 2023 (03:19:16 CEST)

How to cite: Zhang, X.; Liu, M.; Xie, B.; Li, Y.; Hao, Z.; Wang, Z.; Tang, S.; Wang, Y.; Shen, J.; Dai, C. Ellagic Acid Supplementation Ameliorates Cisplatin-Induced Liver Injury in Mice via the Activation of Nrf2/HO-1 Pathway and the Inhibition of NF-kB Pathway. Preprints 2023, 2023100025. https://doi.org/10.20944/preprints202310.0025.v1 Zhang, X.; Liu, M.; Xie, B.; Li, Y.; Hao, Z.; Wang, Z.; Tang, S.; Wang, Y.; Shen, J.; Dai, C. Ellagic Acid Supplementation Ameliorates Cisplatin-Induced Liver Injury in Mice via the Activation of Nrf2/HO-1 Pathway and the Inhibition of NF-kB Pathway. Preprints 2023, 2023100025. https://doi.org/10.20944/preprints202310.0025.v1

Abstract

Cisplatin (CDDP), an important chemotherapeutic agent, could result in potential hepatotoxicity, but the precious molecular mechanisms remain unclear. In this study, the protective effect of ellagic acid (EA) on CDDP exposure-induced hepatotoxicity and underlying molecular mechanisms were investigated using a mouse model. Mice were randomly divided into control, CDDP model, EA100 (i.e., EA 100 mg/kg/day), and CDDP plus EA 25, 50, and 100 mg/kg/day. Mice in all CDDP-treated groups were intraperitoneally injected with CDDP 20 mg/kg/day for 2 days. In all EA co-treatments, mice were orally administrated with EA for 7 days. Our results found that, compared to the control group, CDDP treatment resulted in liver dysfunction, oxidative stress, and hepatocyte necrosis, which are effectively revised by EA supplementation in a dose-dependent manner. Meanwhile, EA supplementation inhibited CDDP-induced the elevation of caspases-9 and -3 activities in the liver tissues of mice. Furthermore, EA supplementation significantly downregulated CDDP exposure-induced the increases of NF-κB, IL-1β, TNF-α, and IL-6 proteins and mRNAs, while further upregulated the expression of Nrf2, and HO-1 proteins and mRNAs. Taken together, our results reveal that EA supplementation could ameliorate CCDP-induced liver injury in mice via the opposite regulation of Nrf2/HO-1 and NF-kB pathways.

Keywords

Ellagic acid; cisplatin; hepatotoxicity; Nrf2/HO-1 pathway; NF-κB pathway

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

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